5-(2-Chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine prepared by the present invention has the following formula (I) and is generally termed Ticlopidine. ##STR1##
Ticlopidine is a compound known, per se, and its pharmacological effects are disclosed in EUR. J. MED. CHEM.-CHIMICA THERAPEUTICA, SEPTEMBER-OCTOBER 1974-9, No. 5, p 487. Because of their anti-inflammatory, vasodilative and platelet agglutination inhibiting activities, in particular, Ticlopidine and its salts are useful as medicines.
The synthetic route of Ticlopidine by reacting 4,5,6,7-tetrahydrothieno[3,2-c]pyridine of the formula (II) ##STR2## with 2-chlorobenzyl halide of the formula (III) ##STR3## wherein X represents Cl, Br or I, has heretofore been known, as disclosed in EUR. J. MED. CHEM.-CHIMICA THERAPEUTICA, SEPTEMBER-OCTOBER 1974-9, No. 5, p 483. In this process, the compound of the formula (II) and the compound of the formula (III) are heated under reflux in ethyl alcohol in the presence of potassium carbonate. The process, however, has such disadvantages that the reaction proceeds rigorously to a considerable extent with the formation of much by-products, and that the subsequent purification of the reaction mixture is complicated and moreover, this reaction gives the desired product in yield as low as about 25%. As an alternative to the above-mentioned process, the aforesaid literature discloses a process (reaction route A as mentioned below) wherein thieno[3,2-c]pyridine is N-benzylated with 2-chlorobenzyl halide of the formula (III) to the corresponding quaternary ammonium salt, followed by reduction with NaBH.sub.4, or a process (reaction route B as mentioned below) wherein 4,5,6,7-tetrahydrothieno[3,2-c]pyridine of the formula (II) is reacted with a highly active 2- chlorobenzoic acid halide, followed by reduction with LiAlH.sub.4. These alternatives, however, have the disadvantages of increased process steps and troublesomeness of manufacture: ##STR4##